Interferon-beta not only inhibits interleukin-1beta and tumor necrosis factor-alpha but stimulates interleukin-1 receptor antagonist production in human peripheral blood mononuclear cells.
Imbalance between pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) and their respective inhibitors is likely to be involved in the pathogenesis of chronic inflammatory disorders such as multiple sclerosis and rheumatoid arthritis. Increasing evidence suggests that the administration of interferon-beta (IFN-beta) displays some efficacy in the treatment of patients with relapsing-remitting multiple sclerosis. The aim of the present study was to determine the effect of IFN-beta on the production of pro-inflammatory cytokines and their inhibitors by stimulated peripheral blood mononuclear cells (PBMC). IFN-beta decreased the production of both IL-1beta and TNF-alpha in a dose-dependent manner, by up to 80% and 55%, respectively. Simultaneously, IFN-beta increased the production of IL-1 receptor antagonist (IL-1Ra) by 37% and did not modulate the release of TNF-soluble receptors (TNF-sRs) p55 and p75. Therefore, by favoring the production of cytokine antagonists over that of pro-inflammatory cytokines, IFN-beta induces an imbalance supporting anti-inflammatory processes. This effect might account for some of the therapeutic benefit of IFN-beta.
Coclet-Ninin
J
J
Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Dayer
J M
JM
Burger
D
D
D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007375:Interleukin-1; D010835:Phytohemagglutinins; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta